Method and apparatus for the ultrasonic cleaning of biofilm coated surfaces

ABSTRACT

To treat body surfaces, such as the sinuses, which are coated with biofilms, the surface is irrigated and suctioned with a fluid which may contain a biocide or other chemical agent for disrupting the biofilm while ultrasonic energy is applied to either the fluid barrier formed over the biofilm or a body surface proximal to the biofilm. Action of the fluid enhanced by the ultrasonic energy tends to remove sections of biofilm which are suctioned out of the site. An electrical field may also be applied to the biofilm to enhance the disruptive action. Apparatus for practicing this method to treat chronic rhinosinusitis comprises an elongated tube adapted to be inserted into sinus cavities through the nose or mouth. The tube includes a first lumen which feeds an irrigating fluid containing biocides and/or biofilm-disruptive chemicals to the treatment site and a second lumen which suctions fluid from the site. An ultrasound horn extends through the tube and its distal end introduces ultrasonic energy into the fluid layer overlying the biofilm. Alternatively, an ultrasound probe may be applied to an adjacent body surface, such as the face over a sinus cavity. In an alternative embodiment, the tube includes a pair of electrodes which establish an electric field across the biofilm, accelerating degradation.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/427,257 filed Apr. 21, 2009, which is a continuation of U.S. patentapplication Ser. No. 11/257,198 filed Oct. 24, 2005, now U.S. Pat. No.7,522,955 which is a continuation-in-part of U.S. patent applicationSer. No. 11/004,392 filed Dec. 3, 2004, which is a continuation-in-partof U.S. patent application Ser. No. 10/955,173 filed Sep. 30, 2004,which claims priority of U.S. Provisional Patent Application Ser. No.60/508,824 filed Oct. 3, 2003, which is incorporated herein byreference. This application is also a continuation of U.S. patentapplication Ser. No. 12/724,306 filed Mar. 15, 2010.

FIELD OF THE INVENTION

This invention relates to methods and apparatus for the ultrasoniccleaning of bodily tissues coated with biofilm and more particularly, tosuch method and apparatus employing irrigation of the biofilm and theapplication of ultrasonic energy to the biofilm.

BACKGROUND OF THE INVENTION

Bacteria may exist within a fluid media in a planktonic state or mayform on a surface bounding the fluid medium in a conglomerate ofmicrobial organisms termed a biofilm. In the biofilm, the bacteria liveat a lower metabolic state than when in planktonic form and exude ahydrated matrix of exopolymers, typically polysaccharides, and othermacromolecules. Bacteria in the biofilm form strong chemical bonds withsurface carbohydrate moieties. The exopolymers encase the bacteria in amanner that leaves tunnels or channels through which the overlying fluidmedium can circulate. In this way, the bacteria are protected from thedangers of the fluid medium, can receive nutrients, and rid themselvesof waste. The protective film formed as part of a biofilm shields thebacteria from the action of antimicrobials and like therapeutic agentsat concentrations which would otherwise normally affect the bacteria.

The bacteria in this unique metabolic state affect other bacteria in theregion to produce a coordinated lifestyle. This process is termed“quorum sensing.”

Biofilms may be formed on the surface of any living tissue, as well asforeign bodies, such as heart valves and the like, which are maintainedin association with human tissues. When the biofilm is formed on livingtissue, the biochemical products and toxic wastes it secretes may affectthe tissue surface to produce an inflammatory state and areas of chronicinfection, such as chronic ear disease, osteomyelitis, chronictonsillitis, prostatitis, vaginitis, and calculi, as in the kidney. Inmany cases, chronic sinusitis appears to be an inflammatory disease ofthe lining mucosal, rather than the disease of bacteria-invading tissue.I have conducted electron microscopic studies that show biofilm existson the mucosal blanket overlying the cilia extending from sinus tissue.Collateral damage from the immune interaction between the biofilmproducts and the associated tissue would be the basis of theinflammatory mucositis seen in chronic rhinosinusitis.

The biofilm insulates the embedded bacteria from biocides contained inthe proximal fluid layer so that normal concentrations of antibiotics orthe like, which would kill the bacteria if they were in a planktonicstate, have little or no effect on the bacteria of a biofilm. Antibioticconcentrations of 1000 to 2000 times higher than possible with systemicapplied antibiotics would be required to destroy the bacteria of abiofilm.

Past efforts to disrupt the biofilm by breaking it up or killing thebacteria have included treatment with chemical compounds such asantibiotics, chemical agents directed at dissolving or breaking up thepolysaccharide binders such as surfactants, enzymes, denaturing agents,and the like. In the dental field, the most effective treatment has beenfound to be scraping and debriding with mechanical instruments. Effortshave also been made to use ultrasonic energy to either increase themetabolic rate of the underlying bacteria so that they better absorbantibiotics and the like, or to mechanically disrupt the biofilmencasement by the mechanical bursting of micro-bubbles induced byultrasonic energy sources. It has also been suggested that electricfields imposed across the biofilms or the fluid layers in contact withthe biofilm will enhance break-up or electrophoretically drive biocidesinto the bacteria encased in the layers.

SUMMARY OF THE INVENTION

The present invention is accordingly directed toward a method ofremoving biofilms in general, and particularly from living tissue, andmore particularly from body cavities that are coated with biofilm, byflowing fluid containing various biofilm-active agents against thebiofilm and suctioning the fluid from the area. Simultaneouslyultrasonic energy is applied to the biofilm either by a probe insertedinto the fluid layer or by application through body tissues from aremote location. The fluid irrigation is introduced under pressure andwithdrawn by a suctioning action to introduce the disruptive materialsto the biofilm and the ultrasound produces shear forces which tend totear off portions of the film and withdraw them from the treatment area.

This irrigation-suction action creates a fluid film over the biofilm andthe ultrasonic energy acts to mechanically drive the fluid into the filmand produce micro-bubbles in the fluid which release energy uponbursting and mechanically disrupt the fluid. Alternatively, theultrasonic energy may increase bacterial metabolism leading tosusceptibility to deranging protein synthesis or cell division. Incertain embodiments of the invention which will subsequently bedescribed in detail, this irrigation/suction accompanied by theintroduction of ultrasonic energy into the resulting film may beaccompanied by electric fields imposed across the biofilm or the fluidinterfacing the biofilm and/or mechanical scrubbing, to further enhancethe breakup of the biofilm.

These actions to disrupt the biofilm are all designed in such a way asto neither destroy nor unduly stress the underlying tissue. In an invitro experiment sinus tissues covered by a mucus blanket harboring abiofilm were treated by irrigation and suction and ultrasonic energy wasintroduced by a probe immersed in the fluid layer covering the tissue.In another experiment the ultrasonic energy was introduced through thewall of the fluid container. In both cases the ultrasonic energy andirrigation shattered and removed the biofilm and the cilia growing fromthe tissue remained intact.

A preferred embodiment of the apparatus for practicing the presentinvention, which will subsequently be described in detail, comprises anelongated tube or barrel, adapted to be introduced to the human bodythrough the nasal passages or otherwise, so that its distal end is inproximity to a biofilm-lined sinus to be treated. The tube may be rigidor flexible, straight or bent, and includes a first lumen forintroducing pressurized bio-treatment fluid at the proximal end so thatit passes through the tube and exits at the distal end. The dischargemay be through a nozzle to produce a high-velocity spray. A second lumenis connected to a vacuum source at the proximal end so as to create asuction at the distal end to remove excess fluid along with debris,including fragments from the biofilm and secretions from the sinuses.Both the irrigation of the bio-affecting fluid and its suctioned removalmay be continuous or intermittent, controlled by valves. This allows theintroduction of fluid pressure waves by the alternate introduction ofpressured fluid and its suctioned removal.

The distal section of the tube may be manually deformable to allow thesurgeon to conform the tube to particular applications. This distalsection may be removable from the main section of the apparatus to allowreplacement with a sanitary, unbent section.

In an alternative embodiment of the invention the ultrasonic energy isintroduced to the distal end of the application tube by introducing theultrasound into the proximal end of the irrigating lumen so that thefluid column in the tube carries the ultrasonic forces to the treatmentarea, eliminating the need for an ultrasound horn formed along thelength of the apparatus.

In an alternative embodiment of the invention, the biofilm affectedtissue may be encased in a chamber having open resilient edges whichbear against the tissue at its boundaries; the bio-affecting fluid isthen introduced and removed from the chamber and ultrasonic forces areimposed on the fluid contained within the chamber, and bearing againstthe biofilm, either by a ultrasonic horn projecting into thefluid-filled cavity, or by the application of ultrasonic forces to thewall of the chamber.

The biofilm encasing chamber may either be formed at the end of anelongated tube containing the fluid lumens and the ultrasonic horn, oras a separate device which may be applied to external body parts, suchas skin burns.

In still another embodiment of the invention the ultrasonic energy isintroduced to the biofilm through the surrounding body structure byapplying energy from an ultrasound probe into a body surface proximal tothe biofilm, through a bag of fluid bearing against that surface. Intreating sinusitis the probe may be positioned on the patient's facenearest the sinus being irrigated. The ultrasonic vibrations passthrough the facial bones and tissue and stimulate the biofilm.

Other objectives, advantages and applications of the present inventionwill be made apparent by the following detailed description of severalembodiments of the invention. The descriptions make reference to theaccompanying drawings in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a handheld instrument, formed inaccordance with the present invention, for practice of the inventivemethod;

FIG. 2 is a cross-sectional view of the tube of the handheld tool ofFIG. 1, taken along line 2-2 of FIG. 1;

FIG. 3 is a cross-sectional view of the device of FIG. 1 inserted into aliving body cavity, with sections broken away to show the constructionof the tube;

FIG. 4 is a cross-sectional view of an alternative embodiment of theapparatus of the present invention inserted into a living body cavity,and partially broken away to exhibit the electrodes used to impose anelectrical field across the biofilm;

FIG. 5 is a cross-sectional view of another alternative embodiment ofthe apparatus of the present invention which includes a biofilm abradingdevice for imparting mechanical energy to the biofilm, supported at thedistal end of the tube;

FIG. 6 is a cross-sectional view of an alternative embodiment of theapparatus of the present invention wherein the ultrasonic generator isdisposed at the distal end of the instrument;

FIG. 7 is a view, partly in section, of an alternative form of theapparatus of the present invention including a cavity adapted tosurround the treatment area;

FIG. 8 is another alternative embodiment of the apparatus of the presentinvention including a cavity adapted to surround the treatment area andhaving inlet and outlet ports for the bio-reducing agent and means forintroducing ultrasonic energy through the wall of the cavity; and

FIG. 9 illustrates a method of treatment of a sinus to remove a biofilmin the mucosal blanket, wherein ultrasonic energy is introduced throughthe head from a facial probe while the sinus cavity is subjected toirrigation and suction via a probe inserted into the cavity.

DETAILED DESCRIPTION OF THE INVENTION

The method of the present invention broadly involves treatment of a bodytissue or bodily implant or prosthesis having a biofilm coating on itssurface by irrigating the surface with a flow of fluid and suctioningthe excess fluid off while imparting energy to the biofilm directly orthrough the fluid to reduce or change the biofilm. The irrigating fluidpreferably contains a bio-reducing agent which will reduce or disruptthe biofilm by destroying its integrity or damaging the constituentbacterial cells. These agents may include surfactants, proteases,enzymes, denaturing agents, and the like. They may include biocides suchas antibiotics and antifungal agents.

The chemical agents which may disrupt and destroy the biofilm includeguaifenesin, dornase alfa and N-acetylcysteine. These materials areparticularly advantageously used in a preferred embodiment of theinvention in which the biofilm and mucus coats the sinuses. Guaifenesinis a mucolytic and is often used for the treatment of sinusitis andrhinitis. Dornase alfa (ymogen) is used to treat the thick mucus ofcystic fibrosis and N-acetylcysteine is used for excess mucus in chronicbronchitis. They are known to break up mucus which is involved inbiofilm infections and may act on the biofilm itself. Thus, the use ofthese chemicals in the method of the present invention performs asynergistic role in simultaneously treating the underlying mucosaltissues and reducing the integrity of the overlying biofilm.

Any other bio-reducing or biocide drugs or combinations thereof may beused in a particular application.

The ultrasonic energy imparted into the fluid film covering the biofilm,in the practice of the present invention, may be of a sinusoidal orpulsed character. The ultrasonic signal is generated by a unit that isexternal of the body. The generator may be of a fixed frequency or itmay scan a range of frequencies continually to ensure optimum couplingof energy through the fluid layer into the biofilm. The exact manner inwhich ultrasonic forces enhance destruction of biofilm may involve thephysical agitation of the minute bubbles produced by the ultrasound inthe overlying fluid. Bursting of these bubbles produces forces that maycause tears in the biofilm. Alternatively, the ultrasonic energy mayincrease the metabolism of the bacteria in the biofilm, increasing itssusceptibility to the biocides and bio-reducing agents in the irrigatingfluid. The energy of the ultrasound must be limited to avoid damage tothe underlying tissues, and values as high as 250 watts per squarecentimeter are apparently safe.

This device is not designed to destroy mucosal tissue. Relatively lowfrequencies have been found more effective than higher frequencies inultrasonic treatment of biofilm and 10 kHz-100 kHz may be a reasonablerange of application. In in vitro experiments I have used 35 kHzsuccessfully.

In those embodiments of the invention in which an electric field isapplied across either the microfilm or the fluid layer overlying themicrofilm, either AC or DC may be applied. The DC may be pulsed so thatrapid changes in the field gradient induce tearing forces in thebiofilm.

A preferred embodiment of an instrument for use in practice of thepresent invention is illustrated in FIG. 1. The instrument, generallyindicated at 10, has a handle section 12 for manual support andmanipulation of the device and an elongated application tube or barrel14 extending from the handle and terminating in a distal end 16. Thetube 14 may be rigid and may be straight or formed with a bend along itslength. Alternatively, it may be made of a manually, deformable materialand may be bent as needed for application into a body cavity. The distalend of the tube 14 may be removable from the handle 12 for replacement.

A pair of conduits 18 extend along the handle and connect at theirproximal end to a source of the bio-affecting irrigating fluid and to asink for the suctioned fluid (not shown). The fluid is pumped outwardlyfrom the proximal end from a source in one conduit and is then carriedby the other conduit back from the irrigated source to the proximal end.

The pump which feeds the irrigating fluid to the instrument 10 and thesuction device that retrieves it from the irrigated area may feed fromthe same sump with an appropriate filter in the return line to removesolid matter contained in the fluid. Alternatively, the fluid may not bereused and the irrigated fluid may be discarded. The two conduits 18feed to lumens in the tube section 14. As is best seen in the crosssection of FIG. 2, the irrigating fluid may pass through a lumen 20which is concentric about the tube 14 along its length and returnthrough a larger lumen 22. An ultrasound horn 24 carries energy from agenerator 50 (FIG. 4) at the proximal end to the distal end.

When used for the treatment of rhinitis, the tube 14 is applied throughthe nasal cavity so that its proximal end is adjacent to the sinus areacoated with biofilm to be treated. Irrigating fluid is then suppliedthrough lumen 20 and withdrawn through lumen 22 at a suitable rate tomaintain a fluid layer over the biofilm area. Ultrasonic energy may beapplied through horn 24 to the fluid layer so that forces are imposed onthe biofilm. Alternatively, in the embodiment of the inventionillustrated in FIG. 9, the ultrasound may be applied separately from theinstrument 10 through the patient's body.

The irrigation produces shear forces which tend to tear the protrudingsections of the biofilm away and the mechanical agitation produced bythe ultrasonic energy enhances this tearing action. The bio-affectingagents in the circulating fluid also act on the biofilm so as to reduceor remove it. The process may require application of combined irrigationand ultrasound for an intended period, such as thirty minutes.

FIG. 3 illustrates the application of a preferred embodiment of themethod of the present invention to a body cavity 30 such as the sinuses.A biofilm coating 32 extends over an infected area, releasing materialswhich inflame the underlying tissue. Irrigating fluid containingbiocides and/or bio-reducing agents are introduced through the lumen 20from a fluid source 46 and withdrawn from the larger area lumen 22 to afluid sink 48. Ultrasonic energy is introduced into the fluid film whichresults from the irrigation via the ultrasonic horn 24 from a generator44. The biofilm is acted on by the physical shearing forces imposed bythe irrigation and suction; by the mechanical forces generated in theoverlying fluid film from the ultrasound: and chemical action takesplace as a result of the agents contained within the irrigating fluid.These factors reduce or completely eliminate the biofilm so as to freethe inflamed area for application of antibiotics and the like which maybe contained in the irrigating fluid or may be introduced separatelyfollowing treatment with the irrigating fluid and ultrasound. Theultrasonic generator 44 provides the energy to the horn either at a setfrequency or a scanned frequency or in pulses.

FIG. 4 illustrates an alternative embodiment of apparatus capable ofimposing an electric field across the biofilm encoating the infectedarea and/or the fluid layer overlying the biofilm. The structure of theapplication tube is identical to the device in FIG. 1 with the exceptionthat a pair of electrodes 40 and 42 extend down diametrically opposedsides of the tube from the proximal end to the distal end. At theproximal end they are connected to an electrical source 50 whichgenerates a potential difference across the electrodes 40 and 42. Theapplied voltage may be either direct current, either constant or pulsed,or alternating current of a fixed or scanned frequency. The applicationdevice also connects to a fluid source 46, a fluid sink 48, and anultrasound generator 44.

The electric field imposes phoretic forces on the biofilm and may drivethe irrigating fluid into the biofilm to enhance disruptive action.

An embodiment of the invention illustrated in FIG. 5 applies mechanicalforces to the biofilm through a brush or abrading device 60. The deviceis either rotated or oscillated through a flexible shaft 62 whichextends through the center of the rod 14. At the proximal end it isdriven by a drive member 64. Irrigating fluid is provided through a line66 from a sump to the lumen 20 of the tube 14 and is returned throughthe lumen 22 to the sump 68 through a filter 70. Ultrasonic forces mayalso be applied through an ultrasonic horn driven by the generator 72.

Alternatively, the ultrasonic forces could be applied to the proximalend of the fluid column formed in the lumen 20 so that the ultrasonicenergy is carried to the distal end 16 by that column, eliminating theneed for an ultrasonic horn. The transmission of ultrasonic forcesthroughout a fluid column is described in ULTRASONICS, VOL. 26, No. 1,1988 at pages 27-30. The electric field applying electrodes 40 and 42 ofthe embodiment of FIG. 4 could also be combined with this unit.

In another alternative version of the instrument 10, illustrated in FIG.6, rather than generating the ultrasonic vibrations at the proximal endand transmitting them through the instrument to the distal end, in themanner of the previously described embodiments, a piezoelectricgenerator 120 is supported at the distal end. Electric signals forpowering the generator 120 are provided by a power source 122, locatedat the proximal end of the instrument 10, and carried to the generator120 by wires 124 extending through the length of the instrument. Thisarrangement lightens the weight of the instrument and eliminates theattenuation of the ultrasonic waves which occurs during transmissionalong the body of the instrument.

The method of the present invention may also be employed on living bodytissues that are easily accessible, such as the outer body covered byskin or the mucous membranes of the oral areas. FIG. 7 illustrates analternative embodiment of the apparatus of the present invention whichcan be used to treat biofilms formed on these accessible areas. Atypical application is to treat a burned portion of the skin over whicha biofilm has formed. The apparatus illustrated in FIG. 7 issubstantially identical to the embodiment of FIG. 1 except for theprovision of a semispherical cavity 80 which is attached to the rod 14adjacent its distal end 20. The cavity has a central hole through whichthe distal end of the rod 14 passes so that the open end of the cavityextends beyond the distal end 20. A resilient gasket 82 is formed aboutthe open edge of the cavity 80. By proper manipulation of the tube 14the gasket may be pressed against an area of the skin to be treated toproduce a closed containment volume 84.

The irrigating flow of fluid containing a biocide or other bio-affectingagent from the rod end 14 fills the volume 84 with fluid. As additionalfluid is introduced the surplus is sucked off through the second lumenof the rod 14. Ultrasonic energy is then introduced into the fluidthrough the horn end 16, causing forces to be imposed on the treatmentarea 86 bounding the volume 84.

A variant of the apparatus used for the treatment of biofilms formed onexterior or otherwise accessible body tissues is illustrated in FIG. 8.A semispherical chamber 92 with a resilient gasket 94 supported on itsedge is brought into contact with a region 90 of the body which iscoated with biofilm so as to define an enclosed volume 96.

The volume 96 is irrigated by fluid following from an input tube 98 andexiting the volume 96 from an outlet tube 100. The irrigating fluidcontains biofilm affecting agents. The resulting fluid in the volume 96is agitated by ultrasonic waves generated by piezoelectric transducers102 and 104 spaced on the wall of the enclosure 92 and energized byappropriate electrical signals.

As has been noted, the ultrasonic energy may be introduced into thebiofilm by means independent of the fluid flow generated by theirrigation apparatus. In the embodiment of the invention illustrated inFIG. 9, a tube 110 is illustrated as being inserted into the nasalcavity of a human head, generally indicated at 112, so that its distalend is adjacent the frontal sinus 114. The tube 110 contains a pair oflumens for introducing under pressure, and removing under suction, anirrigating fluid, preferably containing a biofilm active agent which isthe bio-reducing or biocide drug previously described, onto the mucosalsurface covering the exterior of the frontal sinus. The biofilm has themucosal surface as its substrate and it may become embedded within themucosal surface.

Simultaneous with the irrigation of the mucosal surface overlying thefrontal sinus cavity through the tube 110, ultrasonic energy isintroduced into the exterior of the head, proximal to the location ofthe frontal sinus, through a probe 116 connected to a transducer 118.The probe 116 has a flexible, fluid-filled bag 119 supported on its end.The bag may be filled with a gel, water, or other fluid transparent toultrasonic energy. The bag prevents skin on the head 112 from beingburned by ultrasonic energy. It is positioned in pressured contact withthe head to provide an efficient interface.

The transducer 118 is powered by an ultrasonic generator 120. The powerlevels of the ultrasonic energy are preferably somewhat higher thanthose provided through the tube 110, because of the attenuation of theenergy by the skull bones. The ultrasonic energy reaches the mucosallayer on top of the frontal sinus 114 through the skull and cooperateswith the irrigating fluid in a manner similar to the previouslydescribed embodiments of the invention.

Alternatively, the ultrasonic energy could be introduced at otherlocations on the interior of a nasal cavity adjacent to the sinus 114.In the treatment of other biofilms formed at other locations within thehuman body, similar techniques may be used to provide the ultrasonicenergy independent of the irrigating fluid.

1. The method of treating a sinus within a cavity in a human head, thesinus being covered by mucosal tissue having biofilm thereon,comprising: irrigating the cavity with a fluid containing a biofilmreducing agent; and simultaneously introducing ultrasonic energy intothe biofilm by applying ultrasonic energy to the exterior of the headproximal to the sinus.
 2. The method of claim 1 wherein the biofilmreducing agent constitutes an antibiotic.
 3. The method of claim 1wherein the biofilm active agent also constitutes a mucolytic.
 4. Themethod of claim 3 wherein the mucolytic comprises guaifenesin.
 5. Themethod of claim 3 wherein the mucolytic comprises N-acetylcysteine. 6.The method of claim 1 wherein the ultrasonic energy is applied to theexterior of the head through a fluid interface.
 7. The method of claim 6wherein the fluid interface comprises a fluid filled bag.
 8. The methodof claim 1 wherein the sinus is irrigated through a tube inserted intothe nasal cavity of the head.